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Bioengineered vault nanoparticle immunotherapy for Glioblastoma:
Glioblastoma multiforme (GBM) is the most common and malignant form of primary brain tumor, yet despite the utilization of aggressive surgery, radiation and chemotherapy, the mean survival for patients with this disease is only 14 months. Recent years have seen a blossoming of research addressing the benefits of immunotherapy, as it offers the potential for target specific destruction without damage to normal adjacent tissue. Immunotherapy involves utilizing the body's own immune system to combat brain tumors. Several forms of immunotherapy also act as personalized medicine-a unique therapy tailored for each person's unique brain tumor. It was once thought that there were no immune cells in the brain, but recent research has shown that the brain does have a special distinct immune response. Further translational research into immunotherapy is being done at UCLA to develop effective treatments.
Our lab is one of the only labs in the country to be studying the use of bioengineered vault nanoparticle technology to stimulate the immune system against brain cancer such as GBM. Naturally occurring vaults are proteins that are already organic and natural to human cells. Bioengineered vault nanoparticle vaccines containing immunogenic antigens have recently demonstrated the ability to induce an active immune response against Chlamydia in animal models.
We hypothesize that these nanoparticles, coupled with glioma antigens (GAA), will induce a specific immune response and establish a novel method of immunotherapy for GBM. While investigating this technology, we hope to characterize the feasibility and mechanism behind this technique, and potentially optimize the delivery of a novel and clinically significant approach to immunotherapy. More about nanoparticles >
Recently, cancer stem like cells (CSCs) have been identified as a distinct subpopulation of tumor cells. As glioblastoma multiforme (GBM) CSCs are commonly resistant to chemotherapy and radiotherapy, they may require a novel treatment approach. CD133, also known as prominin-1, is one of the most well-characterized GBM CSC markers. We hypothesize that an effective anti-tumor immune response against GBM CSC populations enriched with CD133 can be characterized and may demonstrate a novel CSC target of immunotherapy for GBM. We will be analyzing the anti-tumor antibody response to CD133+ cells in several primary cultures obtained from tumor samples, as well as from established glioma cell lines in vitro. This will establish the foundation for subsequent in vivo experiments. The feasibility of utilizing a dendritic cell vaccine against GBM to induce an active immune response has already been well established. We will test whether dendritic cells pulsed with CSC GBM lysate will invoke an immune response against GBM in our in vivo tumor model. We ultimately hope to help elucidate the involvement of CSC and CSC markers in GBM development and its potential utilization as an immunotherapeutic target against glioma CSCs.
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